Cargando…
Non-Overlapping Progesterone Receptor Cistromes Contribute to Cell-Specific Transcriptional Outcomes
The transcriptional effects of the ovarian hormone progesterone are pleiotropic, and binding to DNA of the nuclear progesterone receptor (PR), a ligand-activated transcription factor, results in diverse outcomes in a range of target tissues. To determine whether distinct patterns of genomic interact...
Autores principales: | , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3335806/ https://www.ncbi.nlm.nih.gov/pubmed/22545144 http://dx.doi.org/10.1371/journal.pone.0035859 |
_version_ | 1782230856015806464 |
---|---|
author | Clarke, Christine L. Graham, J. Dinny |
author_facet | Clarke, Christine L. Graham, J. Dinny |
author_sort | Clarke, Christine L. |
collection | PubMed |
description | The transcriptional effects of the ovarian hormone progesterone are pleiotropic, and binding to DNA of the nuclear progesterone receptor (PR), a ligand-activated transcription factor, results in diverse outcomes in a range of target tissues. To determine whether distinct patterns of genomic interaction of PR contribute to the cell specificity of the PR transcriptome, we have compared the genomic binding sites for PR in breast cancer cells and immortalized normal breast cells. PR binding was correlated with transcriptional outcome in both cell lines, with 60% of progestin-regulated genes associated with one or more PR binding regions. There was a remarkably low overlap between the PR cistromes of the two cell lines, and a similarly low overlap in transcriptional targets. A conserved PR binding element was identified in PR binding regions from both cell lines, but there were distinct patterns of enrichment of known cofactor binding motifs, with FOXA1 sites over-represented in breast cancer cell binding regions and NF1 and AP-1 motifs uniquely enriched in the immortalized normal line. Downstream analyses suggested that differential cofactor availability may generate these distinct PR cistromes, indicating that cofactor levels may modulate PR specificity. Taken together these data suggest that cell-specificity of PR binding is determined by the coordinated effects of key binding cofactors. |
format | Online Article Text |
id | pubmed-3335806 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-33358062012-04-27 Non-Overlapping Progesterone Receptor Cistromes Contribute to Cell-Specific Transcriptional Outcomes Clarke, Christine L. Graham, J. Dinny PLoS One Research Article The transcriptional effects of the ovarian hormone progesterone are pleiotropic, and binding to DNA of the nuclear progesterone receptor (PR), a ligand-activated transcription factor, results in diverse outcomes in a range of target tissues. To determine whether distinct patterns of genomic interaction of PR contribute to the cell specificity of the PR transcriptome, we have compared the genomic binding sites for PR in breast cancer cells and immortalized normal breast cells. PR binding was correlated with transcriptional outcome in both cell lines, with 60% of progestin-regulated genes associated with one or more PR binding regions. There was a remarkably low overlap between the PR cistromes of the two cell lines, and a similarly low overlap in transcriptional targets. A conserved PR binding element was identified in PR binding regions from both cell lines, but there were distinct patterns of enrichment of known cofactor binding motifs, with FOXA1 sites over-represented in breast cancer cell binding regions and NF1 and AP-1 motifs uniquely enriched in the immortalized normal line. Downstream analyses suggested that differential cofactor availability may generate these distinct PR cistromes, indicating that cofactor levels may modulate PR specificity. Taken together these data suggest that cell-specificity of PR binding is determined by the coordinated effects of key binding cofactors. Public Library of Science 2012-04-24 /pmc/articles/PMC3335806/ /pubmed/22545144 http://dx.doi.org/10.1371/journal.pone.0035859 Text en Clarke, Graham. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Clarke, Christine L. Graham, J. Dinny Non-Overlapping Progesterone Receptor Cistromes Contribute to Cell-Specific Transcriptional Outcomes |
title | Non-Overlapping Progesterone Receptor Cistromes Contribute to Cell-Specific Transcriptional Outcomes |
title_full | Non-Overlapping Progesterone Receptor Cistromes Contribute to Cell-Specific Transcriptional Outcomes |
title_fullStr | Non-Overlapping Progesterone Receptor Cistromes Contribute to Cell-Specific Transcriptional Outcomes |
title_full_unstemmed | Non-Overlapping Progesterone Receptor Cistromes Contribute to Cell-Specific Transcriptional Outcomes |
title_short | Non-Overlapping Progesterone Receptor Cistromes Contribute to Cell-Specific Transcriptional Outcomes |
title_sort | non-overlapping progesterone receptor cistromes contribute to cell-specific transcriptional outcomes |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3335806/ https://www.ncbi.nlm.nih.gov/pubmed/22545144 http://dx.doi.org/10.1371/journal.pone.0035859 |
work_keys_str_mv | AT clarkechristinel nonoverlappingprogesteronereceptorcistromescontributetocellspecifictranscriptionaloutcomes AT grahamjdinny nonoverlappingprogesteronereceptorcistromescontributetocellspecifictranscriptionaloutcomes |